Project I covers the pathology activities essential to the conduct of the Trial. Quality assurance is provided by expert review of all primary tumors from patients entering the Trial, all sentinel/non-sentinel node material from Learning Phase cases and 20% of sentinel modes from Trial Phase cases. To assure uniformity of pathology in the Trial a videotape is provided to all pathologists involved, and annual meetings are held. Dr. Cochran provides help-line support and specific consultation as required. We proposed a detailed study of the amount of distribution of micrometastic and occult melanoma in regional nodes against survival. We will assess whether the sentinel node tumor burden can predict the need for completion lymphadenectomy. We will investigate the frequency and extent of immune modulation of sentinel nodes and relate this to outcome and extent of tumor penetration of the regional nodes. We will undertake a major study to determine whether our present sampling is sufficient. We will assess whether molecular biological techniques improve the accuracy of nodal evaluation over immunohistochemistry. We will continue to develop techniques to allow microscopic confirmation a node is sentinel. We will evaluate the accuracy of our newly developed prognostic models to determine their accuracy on an individual patient basis.